Beta-lactam antibiotics, which generally are penicillins and cephalosporins, have been widely used in the treatment of infections, primarily bacterial, in mammals such as man. Certain micro-organisms are believed to be resistant to these antibiotics because they produce an enzyme, beta-lactamase, which attacks the beta-lactam ring of the antibiotic thereby rendering the drug ineffective.
Barth, in U.S. Pat. No. 4,234,579, has disclosed that 4,4-dioxopenicillanic acid (penicillanic acid 1,1-dioxide) and esters thereof which are readily hydrolyzable in vivo, have antibacterial activity and inhibit microbial beta-lactamases. Barth's inhibitors can be combined with beta-lactam antibiotics to obtain compositions of enhanced effectiveness against microorganisms normally resistant to treatment with the antibiotic alone.
The ester derivatives of 4,4-dioxopenicillanic acid are normally insoluble in aqueous solutions. In some instances, particularly for oral administration, it would be desirable to have a prodrug of 4,4-dioxopenicillanic acid which is water soluble.